The protein encoded by this gene is a cytosolic protein which contains a phosphotyrosine binding (PTD) domain. The PTD domain has been found to interact with the cytoplasmic tail of the LDL receptor. Mutations in this gene lead to LDL receptor malfunction and cause the disorder autosomal recessive hypercholesterolaemia. [provided by RefSeq, Jul 2008] See more...

Aliases for LDLRAP1 Gene

Aliases for LDLRAP1 Gene

  • Low Density Lipoprotein Receptor Adaptor Protein 1 2 3 5
  • Low Density Lipoprotein Receptor Adapter Protein 1 3 4
  • Autosomal Recessive Hypercholesterolemia Protein 3 4
  • ARH 3 4
  • Autosomal Recessive Hypercholesterolemia 2
  • LDL Receptor Adaptor Protein 3
  • FHCB1 3
  • FHCB2 3
  • FHCL4 3
  • ARH1 3
  • ARH2 3

External Ids for LDLRAP1 Gene

Previous GeneCards Identifiers for LDLRAP1 Gene

  • GC01P025742
  • GC01P025870
  • GC01P024124

Summaries for LDLRAP1 Gene

Entrez Gene Summary for LDLRAP1 Gene

  • The protein encoded by this gene is a cytosolic protein which contains a phosphotyrosine binding (PTD) domain. The PTD domain has been found to interact with the cytoplasmic tail of the LDL receptor. Mutations in this gene lead to LDL receptor malfunction and cause the disorder autosomal recessive hypercholesterolaemia. [provided by RefSeq, Jul 2008]

GeneCards Summary for LDLRAP1 Gene

LDLRAP1 (Low Density Lipoprotein Receptor Adaptor Protein 1) is a Protein Coding gene. Diseases associated with LDLRAP1 include Hypercholesterolemia, Familial, 4 and Homozygous Familial Hypercholesterolemia. Among its related pathways are Lipoprotein metabolism and Endocytosis. Gene Ontology (GO) annotations related to this gene include phosphatidylinositol-4,5-bisphosphate binding and amyloid-beta binding. An important paralog of this gene is NUMBL.

UniProtKB/Swiss-Prot Summary for LDLRAP1 Gene

  • Adapter protein (clathrin-associated sorting protein (CLASP)) required for efficient endocytosis of the LDL receptor (LDLR) in polarized cells such as hepatocytes and lymphocytes, but not in non-polarized cells (fibroblasts). May be required for LDL binding and internalization but not for receptor clustering in coated pits. May facilitate the endocytocis of LDLR and LDLR-LDL complexes from coated pits by stabilizing the interaction between the receptor and the structural components of the pits. May also be involved in the internalization of other LDLR family members. Binds to phosphoinositides, which regulate clathrin bud assembly at the cell surface. Required for trafficking of LRP2 to the endocytic recycling compartment which is necessary for LRP2 proteolysis, releasing a tail fragment which translocates to the nucleus and mediates transcriptional repression (By similarity).

Gene Wiki entry for LDLRAP1 Gene

Additional gene information for LDLRAP1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for LDLRAP1 Gene

Genomics for LDLRAP1 Gene

GeneHancer (GH) Regulatory Elements for LDLRAP1 Gene

Promoters and enhancers for LDLRAP1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH01J025542 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 505.7 +0.0 21 4 HNRNPK POLR2G PHF8 ZFX POLR2A ZBTB11 ZNF423 ZBTB26 TARDBP TOE1 LDLRAP1 ZNF593 ENSG00000233478 ENSG00000225643
GH01J025559 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 526.6 +18.3 18276 4.1 ZNF639 EP300 CTBP1 ZNF341 RBM25 NFIC ZKSCAN1 ARNT MEF2B NBN LDLRAP1 ENSG00000225891 ENSG00000233478 LIN28A ENSG00000225643 SDHDP6 TMEM50A
GH01J025565 Promoter/Enhancer 1.6 Ensembl ENCODE CraniofacialAtlas dbSUPER 30 +24.0 24047 5.8 ZNF217 CTCF USF1 GTF2E2 JUND FOS ZNF639 ZNF10 ZIC2 ZBTB10 LDLRAP1 ENSG00000225643
GH01J025573 Enhancer 0.9 ENCODE dbSUPER 14 +30.3 30309 1.2 ZNF217 ZIC2 KDM5B CTCF CEBPB USF1 CEBPG GATA3 MAX MYC LDLRAP1 ENSG00000225643
GH01J025520 Enhancer 0.9 Ensembl ENCODE dbSUPER 12.6 -22.9 -22879 0.6 CTCF REST RAD21 TRIM22 SMC3 FOSL1 ZNF395 ZNF654 ADNP NFATC3 piR-43107-003 LDLRAP1 SELENON ENSG00000233478
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around LDLRAP1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for LDLRAP1

Top Transcription factor binding sites by QIAGEN in the LDLRAP1 gene promoter:
  • AP-2alpha
  • AP-2alpha isoform 2
  • AP-2alpha isoform 3
  • AP-2alpha isoform 4
  • AP-2alphaA
  • E47
  • ITF-2
  • Pax-4a
  • Tal-1
  • Tal-1beta

Genomic Locations for LDLRAP1 Gene

Genomic Locations for LDLRAP1 Gene
chr1:25,543,580-25,591,287
(GRCh38/hg38)
Size:
47,708 bases
Orientation:
Plus strand
chr1:25,870,071-25,895,377
(GRCh37/hg19)
Size:
25,307 bases
Orientation:
Plus strand

Genomic View for LDLRAP1 Gene

Genes around LDLRAP1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
LDLRAP1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for LDLRAP1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LDLRAP1 Gene

Proteins for LDLRAP1 Gene

  • Protein details for LDLRAP1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q5SW96-ARH_HUMAN
    Recommended name:
    Low density lipoprotein receptor adapter protein 1
    Protein Accession:
    Q5SW96
    Secondary Accessions:
    • A2BHI5
    • Q6TQS9
    • Q8N2Y0
    • Q9UFI9

    Protein attributes for LDLRAP1 Gene

    Size:
    308 amino acids
    Molecular mass:
    33885 Da
    Quaternary structure:
    • Interacts (via PID domain) with LDLR (via NPXY motif) (PubMed:12221107). Binds to soluble clathrin trimers (PubMed:12221107). Interacts with AP2B1; the interaction mediates the association with the AP-2 complex (PubMed:12221107). Interacts with VLDLR (By similarity). Interacts with LRP2 (By similarity).

    Three dimensional structures from OCA and Proteopedia for LDLRAP1 Gene

neXtProt entry for LDLRAP1 Gene

Post-translational modifications for LDLRAP1 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for LDLRAP1 Gene

Domains & Families for LDLRAP1 Gene

Gene Families for LDLRAP1 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins

Protein Domains for LDLRAP1 Gene

Blocks:
  • Phosphotyrosine interaction domain
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for LDLRAP1 Gene

GenScript: Design optimal peptide antigens:
  • Autosomal recessive hypercholesterolemia protein (ARH_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q5SW96

UniProtKB/Swiss-Prot:

ARH_HUMAN :
  • The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1.
Domain:
  • The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1.
  • The PID domain mediates interaction with the NPXY internalization motif of LDLR.
genes like me logo Genes that share domains with LDLRAP1: view

Function for LDLRAP1 Gene

Molecular function for LDLRAP1 Gene

UniProtKB/Swiss-Prot Function:
Adapter protein (clathrin-associated sorting protein (CLASP)) required for efficient endocytosis of the LDL receptor (LDLR) in polarized cells such as hepatocytes and lymphocytes, but not in non-polarized cells (fibroblasts). May be required for LDL binding and internalization but not for receptor clustering in coated pits. May facilitate the endocytocis of LDLR and LDLR-LDL complexes from coated pits by stabilizing the interaction between the receptor and the structural components of the pits. May also be involved in the internalization of other LDLR family members. Binds to phosphoinositides, which regulate clathrin bud assembly at the cell surface. Required for trafficking of LRP2 to the endocytic recycling compartment which is necessary for LRP2 proteolysis, releasing a tail fragment which translocates to the nucleus and mediates transcriptional repression (By similarity).

Phenotypes From GWAS Catalog for LDLRAP1 Gene

Gene Ontology (GO) - Molecular Function for LDLRAP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001540 amyloid-beta binding IPI 12805363
GO:0001784 phosphotyrosine residue binding IDA 12451172
GO:0005515 protein binding IPI,IEA 12221107
GO:0005546 phosphatidylinositol-4,5-bisphosphate binding IDA 12451172
GO:0030159 receptor signaling complex scaffold activity IMP 15166224
genes like me logo Genes that share ontologies with LDLRAP1: view
genes like me logo Genes that share phenotypes with LDLRAP1: view

Human Phenotype Ontology for LDLRAP1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for LDLRAP1 Gene

MGI Knock Outs for LDLRAP1:

Animal Model Products

  • Taconic Biosciences Mouse Models for LDLRAP1

CRISPR Products

miRNA for LDLRAP1 Gene

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LDLRAP1

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for LDLRAP1 Gene

Localization for LDLRAP1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for LDLRAP1 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for LDLRAP1 gene
Compartment Confidence
plasma membrane 5
endosome 5
cytosol 5
cytoskeleton 4
extracellular 2
mitochondrion 2
nucleus 2
lysosome 2
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for LDLRAP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005769 early endosome IDA,IEA 14528014
GO:0005829 cytosol IDA 12451172
GO:0005883 neurofilament ISS,IEA 17727637
GO:0005886 plasma membrane TAS --
genes like me logo Genes that share ontologies with LDLRAP1: view

Pathways & Interactions for LDLRAP1 Gene

genes like me logo Genes that share pathways with LDLRAP1: view

Pathways by source for LDLRAP1 Gene

1 GeneGo (Thomson Reuters) pathway for LDLRAP1 Gene
  • Cholesterol and Sphingolipids transport / Influx to the early endosome in lung (normal and CF)

Gene Ontology (GO) - Biological Process for LDLRAP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006629 lipid metabolic process IEA --
GO:0006897 endocytosis IEA --
GO:0006898 receptor-mediated endocytosis IDA 14528014
GO:0008202 steroid metabolic process IEA --
GO:0008203 cholesterol metabolic process NAS 12451172
genes like me logo Genes that share ontologies with LDLRAP1: view

No data available for SIGNOR curated interactions for LDLRAP1 Gene

Drugs & Compounds for LDLRAP1 Gene

(1) Drugs for LDLRAP1 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for LDLRAP1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with LDLRAP1: view

Transcripts for LDLRAP1 Gene

mRNA/cDNA for LDLRAP1 Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LDLRAP1

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for LDLRAP1 Gene

No ASD Table

Relevant External Links for LDLRAP1 Gene

GeneLoc Exon Structure for
LDLRAP1

Expression for LDLRAP1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for LDLRAP1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for LDLRAP1 Gene

This gene is overexpressed in Brain - Cerebellum (x4.8) and Brain - Cerebellar Hemisphere (x4.2).

Protein differential expression in normal tissues from HIPED for LDLRAP1 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (16.2), Platelet (15.3), CD4 Tcells (8.0), Pancreas (7.2), and CD8 Tcells (6.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for LDLRAP1 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for LDLRAP1

SOURCE GeneReport for Unigene cluster for LDLRAP1 Gene:

Hs.590911

mRNA Expression by UniProt/SwissProt for LDLRAP1 Gene:

Q5SW96-ARH_HUMAN
Tissue specificity: Expressed at high levels in the kidney, liver, and placenta, with lower levels detectable in brain, heart, muscle, colon, spleen, intestine, lung, and leukocytes.

Evidence on tissue expression from TISSUES for LDLRAP1 Gene

  • Nervous system(4.9)
  • Skin(2.9)
  • Pancreas(2.2)
  • Blood(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for LDLRAP1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • skeleton
Regions:
Head and neck:
  • ear
  • eye
  • eyelid
  • face
  • head
Thorax:
  • heart
Abdomen:
  • duodenum
  • intestine
  • liver
  • small intestine
General:
  • blood
  • blood vessel
  • skin
  • white blood cell
genes like me logo Genes that share expression patterns with LDLRAP1: view

No data available for Protein tissue co-expression partners for LDLRAP1 Gene

Orthologs for LDLRAP1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for LDLRAP1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia LDLRAP1 31 30
  • 99.23 (n)
OneToOne
cow
(Bos Taurus)
Mammalia LDLRAP1 31 30
  • 90.26 (n)
OneToOne
dog
(Canis familiaris)
Mammalia LDLRAP1 31 30
  • 89.61 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Ldlrap1 17 31 30
  • 86.21 (n)
rat
(Rattus norvegicus)
Mammalia Ldlrap1 30
  • 85.67 (n)
oppossum
(Monodelphis domestica)
Mammalia LDLRAP1 31
  • 85 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia LDLRAP1 31
  • 60 (a)
OneToOne
chicken
(Gallus gallus)
Aves LDLRAP1 31 30
  • 71.13 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia LDLRAP1 31
  • 89 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia ldlrap1 30
  • 65.8 (n)
Str.11033 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.8355 30
zebrafish
(Danio rerio)
Actinopterygii ldlrap1b 31 30
  • 67.88 (n)
OneToMany
ldlrap1a 31
  • 64 (a)
OneToMany
sbcb50 30
Species where no ortholog for LDLRAP1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for LDLRAP1 Gene

ENSEMBL:
Gene Tree for LDLRAP1 (if available)
TreeFam:
Gene Tree for LDLRAP1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for LDLRAP1: view image

Paralogs for LDLRAP1 Gene

genes like me logo Genes that share paralogs with LDLRAP1: view

Variants for LDLRAP1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for LDLRAP1 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
468289 Benign: not provided 25,563,697(+) CA/TG MISSENSE_VARIANT
641308 Uncertain Significance: Familial hypercholesterolemia 4 25,563,754(+) C/T MISSENSE_VARIANT
642366 Uncertain Significance: Familial hypercholesterolemia 4 25,557,205(+) G/A MISSENSE_VARIANT
646841 Uncertain Significance: Familial hypercholesterolemia 4; not provided 25,553,955(+) C/T MISSENSE_VARIANT
648414 Uncertain Significance: Familial hypercholesterolemia 4 25,554,060(+) C/G MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for LDLRAP1 Gene

Structural Variations from Database of Genomic Variants (DGV) for LDLRAP1 Gene

Variant ID Type Subtype PubMed ID
nsv480715 CNV novel sequence insertion 20440878

Variation tolerance for LDLRAP1 Gene

Residual Variation Intolerance Score: 56.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.96; 49.46% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for LDLRAP1 Gene

Human Gene Mutation Database (HGMD)
LDLRAP1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
LDLRAP1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for LDLRAP1 Gene

Disorders for LDLRAP1 Gene

MalaCards: The human disease database

(11) MalaCards diseases for LDLRAP1 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

ARH_HUMAN
  • Hypercholesterolemia, autosomal recessive (ARH) [MIM:603813]: A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins. {ECO:0000269 PubMed:11326085}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for LDLRAP1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with LDLRAP1: view

No data available for Genatlas for LDLRAP1 Gene

Publications for LDLRAP1 Gene

  1. Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein. (PMID: 11326085) Garcia CK … Hobbs HH (Science (New York, N.Y.) 2001) 3 4 23 54
  2. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41 54
  3. A novel Thr56Met mutation of the autosomal recessive hypercholesterolemia gene associated with hypercholesterolemia. (PMID: 20124734) Harada K … Morisaki T (Journal of atherosclerosis and thrombosis 2010) 3 4 54
  4. Prevalence and clinical features of heterozygous carriers of autosomal recessive hypercholesterolemia in Sardinia. (PMID: 19477448) Filigheddu F … Arca M (Atherosclerosis 2009) 3 41 54
  5. Autosomal recessive hypercholesterolemia in Spanish kindred due to a large deletion in the ARH gene. (PMID: 17686643) Quagliarini F … Arca M (Molecular genetics and metabolism 2007) 3 23 54

Products for LDLRAP1 Gene

Sources for LDLRAP1 Gene